Molecular cloning and localization of human atrophin-1-like gene

Through the analysis of EST (Expressed Sequence Tag) database, 25 human EST s with significant similarity to human atrophin-1 gene, which is responsibl e for dentatorubral pallidoluysian atrophy (DRPLA), were as sembled into 5 contigs. Based upon three of these contigs, three probes were designed to s creen the human cDNA Libraries and genomic DNA libraries. Sequences of the cDNA clones obtained from heart and testis cDNA libraries were assembled in to a 4.6 kb cDNA sequence (termed atrophin-1 like gene, ATN1L) which contai ned a complete open reading frame putatively encoded 1012 amino acids. The coding region is composed of 9 exons. Both cDNA and deduced protein sequenc e share striking similarity with human atrophin-1 and rat atrophin-1-relate d gene and protein. Comparative analysis also indicated that C-terminus of the protein was more conservative than its N-terminus. It was a strongly hy drophilic protein with two regions of alternating acidic and basic amino ac id residues as the human atrophin-1 and rat atrophin-1 related protein were . We further mapped this gene to chromosome 1p36 by fluorescence in situ hy bridization.