GENETIC AND PHYSICAL MAPPING OF THE PROGRESSIVE EPILEPSY WITH MENTAL-RETARDATION (EPMR) LOCUS ON CHROMOSOME 8P

Progressive epilepsy with mental retardation (EPMR) is an autosomal re cessive disorder discovered recently from an isolated region in Finlan d. The disorder is characterized by normal early development, generali zed tonic-clonic seizures with onset at 5-10 years of age, and progres sive mental retardation beginning 2-5 years after the onset of seizure s. We recently mapped the EPMR locus to a 7-cM region on chromosome 8p between markers AFM185xb2 and D8S262. A recombination detected with a new microsatellite marker AFMa054td9 narrows the region to 4 cM. A ye ast artificial chromosome (YAC) contig containing 22 YACs was construc ted across the disease gene region. The YAC contig is characterized by a collection of 19 YAC-end sequence-tag sites together with seven mic rosatellite markers. The entire YAC, contig spans a minimum of 3 Mb. M oreover, the distal end of the contig contains a subtelomeric YAC yRM2 205 that anchors the contig to the telomere. Construction of a YAC con tig across the disease gene region is an essential step toward the iso lation of the EPMR gene.