JH8,a Gene Highly Homologous to the MousejerkyGene, Maps to the Region for Childhood Absence Epilepsy on 8q24

Abstract

Insertional inactivation of thejerkygene in transgenic mice resulted epileptic seizures, suggesting that thejerkygene was responsible for mouse epilepsy. To isolate a human homologue of thejerkygene, we screened an Expressed Sequence Tag (EST) database using the cDNA sequence of the mousejerkygene and identified several EST clones which contained homologous sequences to mousejerkygene. Using a clone which showed highest homology as a probe, we isolated cDNA clones from a human fetal brain cDNA library. Sequence analysis of these clones namedJH8(jerkyhomologue of Human on chromosome 8) indicated that it encoded a putative protein with 520 amino acid residues. TheJH8gene has 77% identity to the mousejerkygene at the DNA level, and its protein has 76% identity and 84% similarity to the mouse protein at the amino acid level. Northern blot analysis showed that theJH8gene is expressed ubiquitously with a major transcript of about 9.5 kb in size. Fluorescencein situHybridization (FISH) analysis and radiation hybrid panel mapping revealed that theJH8gene was located on chromosome band 8q24.3 in a region that was syntenic to mouse chromosome 15, the mapping site of the mousejerkygene. Childhood Absence Epilepsy (CAE), one type of Idiopathic Generalized Epilepsy (IGE), has been mapped to chromosome 8q24.3 by linkage analysis. These results suggest thatJH8is a strong candidate gene for CAE.