Insertional inactivation of the jerky gene in transgenic mice resulted epileptic seizures, suggesting that the jerky gene was responsible for mouse epilepsy. To isolate a human homologue of the jerky gene, we screened an Expressed Sequence Tag (EST) database using the cDNA sequence of the mouse jerky gene and identified several EST clones which contained homologous sequences to mouse jerky gene. 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 named JH8 (jerky homologue of Human on chromosome 8) indicated that it encoded a putative protein with 520 amino acid residues. The JH8 gene has 77% identity to the mouse jerky gene 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 the JH8 gene is expressed ubiquitously with a major transcript of about 9.5 kb in size. Fluorescence in situ Hybridization (FISH) analysis and radiation hybrid panel mapping revealed that the JH8 gene was located on chromosome band 8q24.3 in a region that was syntenic to mouse chromosome 15, the mapping site of the mouse jerky gene. Childhood Absence Epilepsy (CAE), one type of Idiopathic Generalized Epilepsy (IGE), has been mapped to chromosome 8q24.3 by linkage analysis. These results suggest that JH8 is a strong candidate gene for CAE.
Copyright 1998 Academic Press.