THE GENOMIC ANALYSIS OF HUMAN DAN GENE

DAN gene is shown to be localized at human chromosome 1p36.11-p36.13, which resides within the consensus deletion observed in neuroblastoma, In the present study, we have isolated the genomic DNA containing the entire human DAN gene and determined its nucleotide sequence, Structu ral analysis revealed that DAN gene is composed of four exons and span s approximately 15 kb, Its overall structure was basically the same as that of rat DAN gene, Two distinct transcription initiation sites (ma jor and minor) were identified by the primer extension experiment, Put ative TATA and CAAT-like elements are present 38 and 366 bp upstream f rom the major transcription start site, respectively, however, no appa rent TATA-like sequence was found in the upstream region of the minor transcription start site, The 400-bp region immediately upstream from the major transcription initiation site was strongly GC-rich (79% GC), Genomic Southern experiments demonstrated that the allelic loss of DA N gene might occur in neuroblastoma, Interestingly, there exist two di nucleotide repeats, (CA)(7) and (CA)(8), in the first intron of DAN ge ne, raising the possibility to distinguish two alleles of DAN gene in some of the cancer cells.