Genetic susceptibility and severity of alopecia areata in human and animalmodels

Alopecia areata (AA) is a non-scarring, inflammatory form of hair loss. Hum an and animal model observations suggest that AA is an autoimmune mediated disease. Genetic influence has been clearly demonstrated in many other auto immune diseases and one would expect that AA is no exception. AA in rodent models involves genetic susceptibility and it is possible to cross breed th e AA phenotype to unrelated rodent strains. Segregation analysis of rodent breeding programs suggests the involvement of several dominant and secondar y genes. The increased frequency of AA in genetically related individuals, suggests that human AA expression also involves genetic susceptibility. Wit hin the general population, AA does not segregate as a Mendelian, monogenic trait. AA is a continuous trait with varying degrees of hair loss within t he affected population. This suggests that human AA expression involves a c omplex interaction of multiple genes. AA is most likely a polygenic disease where several, potentially identifiable, major genes affect disease suscep tibility and minor severity modifying genes may further affect the phenotyp e. Here we review the literature on humans and animal models for AA to iden tify data in support of AA as a polygenic, multivariate penetrance disease with a threshold level for disease onset. Genome wide allelic association s creening of animal models and genetically related human sibling pairs may b e a suitable approach to identifying susceptibility and severity modifying genes for AA.