Genetics of asthma: a primer.

Despite intense research, the morbidity and mortality of asthma remain relatively high. The key reason for this high morbidity and mortality is that the fundamental mechanisms predisposing individuals to the development of asthma are not understood. One approach to discovering fundamental mechanisms is to examine the genetic basis of the disease, with the hope that uncovering the molecular defects will lead to a greater understanding of asthma and improved therapy. This task is difficult with asthma due to its complex nature - there is no gold standard for the diagnosis of asthma, there is a very strong environmental influence and inheritance does not follow classical Mendelian patterns. A number of studies, including studies of twins, indicate that the inheritability estimates for asthma are approximately 30% to 60%. There are two general approaches to identification of genes that predispose individuals to asthma - the candidate gene approach and positional cloning. The candidate gene approach utilizes the available information about the biochemical basis of asthma to identify genes that code for relevant proteins. The positional cloning approach uses DNA markers that have polymorphisms in the population. No specific knowledge of the underlying biology is required; the technique is based on the fact that during meiosis, regions of DNA that are close to one another tend to remain close after recombination. Over the past few years, tremendous strides have been made in identifying regions on the human genome that contain genes that predispose patients to asthma. Discovering such genes will help in development of diagnostic tests, will lead to the use of pharmacogenetics to ascertain optimal therapy for each individual patient and should lead to the discovery of novel drugs that specifically target the abnormality discovered in the genetic studies.