Studying the Genetic Pathogenesis of Atopy and Asthma: Future Directions for Research

Ammar K. Daoud

Abstract


Atopy as a group of diseases is increasing in its prevalence worldwide, which is drawing much interest into its pathogenesis. However, it is frustrating that its pathogenesis is not simple or clear, like many other complex diseases like diabetes mellitus or ischemic heart disease. One thing that is simple and clear is that both genetic or inherited traits and environmental exposures play important roles in the phenotypes that we see. What factors of each type, how many are needed and how they interact are the complex questions that will be answered by reviewing the literature in this article.

Most diseases do not follow a simple Mendelian genetic of autosomal, X linked dominant or recessive design (although there is the question of penetrance in the phenotype for the same genotype). So to solve this type of problem one has to have a good understanding of the models and tools used in the studies and the strengths and weaknesses of each study design. This understanding is vital to simplify the complexities that we see in the medical literature nowadays in the immunology and genetics fields.

For example, to understand from where the name ‘major histocompatibility complex’ genes came from one needs to understand a few deeper points. For the experimental design in inbred strains of mice skin transplantation (which are all identical twins for other mice of the same strain and are homozygous for all genetic loci), it was estimated that there are 50 genes responsible for the graft rejection phenomena. So when the HLA antigens locus was found with its 18 slots for alleles, the name ‘major histocompatibility complex’ became simple and understood although no minor ones were found later.

This review article walks through the models of experiments that tried to explain genetic pathogenesis of asthma and atopy and the technological tools and statistical models used in them. Some recent studies have been listed using each model.

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