This is a pilot grant to examine the genetic basis of alopecia areata. The overall goal of this project is to determine if candidate genes play a substantial role in development of alopecia areata in the general population. We will examine ten microsatellite markers at or near candidate loci including the human homolog to the mouse hairless gene on 8p12. A recent study of two consanguineous families with alopecia universalis showed that mutations in the hairless gene were causitive of the phenotype, the first demonstration that the spectrum of alopecia disorders is mediated via genes. The phenotype in these families is atypical of the alopecia spectrum in that there was no immune involvement. We intend to extend these analyses to a more substantive dataset from the general population to determine if the locus on chromosome 8 and other loci such as HLA have a substantial impact in the etiology of alopecia areata. We will collect data on families with at least two affected members. Since little is known about the genetic architecture of alopecia areata families, we will utilize both model- based and model-free approaches to genetic linkage analysis to evaluate phenotypic data. If we obtain evidence for linkage we will use linkage disequilibrium analysis for fine mapping. Family-based association testing methods will be used to evaluate if any of the markers tested are in fact at the susceptibility gene or at least in very close proximity to the susceptibility gene for alopecia. This application is intended to provide a core for a further, more extensive, acquisition of alopecia phenotype and genotype data. We, ultimately, intend to expand the entire population to include a genome scan and to positionally clone genes for alopecia.
