Localization of the EPM1 gene for progressive myoclonus epilepsy on chromosome 21: linkage disequilibrium allows high resolution mapping

Abstract

The gene for Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) has previously been mapped by linkage to markers on chromosome 21q22.3. By analyzing crossover events in multiplex disease families with newly detected markers from the region we were able to narrow the localization of EPM1 to an interval of approximately 7 cM, between loci D21S212 and CD18. To further refine the localization of the EPM1 gene we applied linkage disequilibrium mapping in 38 Finnish families, consisting of 12 with multiple affected children and 26 with a single affected child. Based on existing knowledge about the structure and history of the isolated Finnish population, we estimated genetic distances based on strong linkage disequilibrium to several marker loci and found that EPM1 resides within 0.3 cM or less of loci PFKL, D21S25 and D21S154. As this genetic distance translates into a likely physical distance of 300 kb or less, these data provide a basis for highly focused attempts to clone EPM1.