Toxicity to man-made products and chemicals may include damage to all human organ system. While dermal toxicity does not often include the mortality that can accompany other organ toxicity, it does involve significant morbidity, as well as personal and societal costs. Irritant contact dermatitis (ICD) is the most common type of chemically-induced cutaneous toxicity and an extremely common malady. Based on skin disease reporting, the prevalence of ICD ranges from 1 - 10%, but it is speculated to be much higher, approaching 25%, in industrialized societies like the United States. It is extremely important to health in the work place, since it represents the most common single occupational disease seen int he United States. Despite it importance, based on sheer numbers of individuals involved, very little is known about the mechanism of development of the inflammatory response to chemical contact which occurs in ICD. A small number of studies, as well as clinical experience, dictates that host factors play an important role in determining which individuals will develop the response. Discerning susceptibility before exposure to irritants in the work place could result in a significant disease in the personal morbidity and societal costs of occupational irritant hand dermatitis. Complex traits are characterized by the fact that mode of inheritance does not follow any of the known Mendelian forms. We will search for genes underlying complex traits, such as ICD, using nonparametric linkage analysis methods, in which no assumptions are made on mode of inheritance of the trait. Therefore, we propose: 1. To ascertain affected sib pairs (ASP) with ICD of the hands due to work place exposure to irritants. 2. To identify ICD susceptibility gene loci by genome wide screening and linkage analysis. 3. To identify, by physical mapping and positional cloning, candidate susceptibility genes for ICD. ?
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