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

Through the analysis of EST (Expressed Sequence Tag) database, 25 human ESTs with significant similarity to human atrophin-1 gene, which is responsible for dentatorubral pallidoluysian atrophy (DRPLA), were assembled into 5 contigs. Based upon three of these contigs, three probes were designed to screen the human cDNA libraries and genomic DNA libraries. Sequences of the cDNA clones obtained from heart and testis cDNA libraries were assembled into a 4.6 kb cDNA sequence (termed atrophin-1 like gene, ATN1L) which contained a complete open reading frame putatively encoded 1012 amino acids. The coding region is composed of 9 exons. Both cDNA and deduced protein sequence share striking similarity with human atrophin-1 and rat atrophin-1-related gene and protein. Comparative analysis also indicated that C-terminus of the protein was more conservative than its N-terminus. It was a strongly hydrophilic protein with two regions of alternating acidic and basic amino acid 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 hybridization.