The genomic analysis of human DAN gene.

Abstract

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. Structural analysis revealed that DAN gene is composed of four exons and spans approximately 15 kb. Its overall structure was basically the same as that of rat DAN gene. Two distinct transcription initiation sites (major and minor) were identified by the primer extension experiment. Putative TATA and CAAT-like elements are present 38 and 366 bp upstream from the major transcription start site, respectively, however, no apparent 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 DAN gene might occur in neuroblastoma. Interestingly, there exist two dinucleotide repeats, (CA)7 and (CA)8, in the first intron of DAN gene, raising the possibility to distinguish two alleles of DAN gene in some of the cancer cells.