A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome 21q22.2

Based on a detailed sequence of the distal Down syndrome critical region (D SCR), we predicted and molecularly cloned a novel gene, designated DSCR5. W e determined the sequences of expressed sequence tags (ESTs) that almost ma tched the predicted cDNA sequence of DSCR5. Northern blot analysis showed t hat DSCR5 is expressed in several tissues including the liver, skeletal mus cle, heart, pancreas and testis. To determine the 5'-end of DSCR5, the olig o-capping method was employed. Combining the EST sequence data and that fro m the oligo-capping experiments, we obtained the full-length cDNA sequence of DSCR5. DSCR5 had at least four types of alternatively spliced variants. According to the number of exons, they could be classified into two subtype s: DSCR5 alpha and DSCR5 beta. DSCR5 alpha includes three splice variant su btypes, DSCR5 alpha 1, alpha 2 and alpha 3 which each has different first n on-coding exon. In addition, the most abundantly isolated form, DSCR5 alpha 1, shows microheterogeneity of the mRNA start site. Comparison of the sequ ences between the predicted cDNA and the molecularly cloned cDNA revealed t hat the computer programs had limited validity to correctly predict the ter minal exons. Thus, molecular cloning should always be required to complemen t the inadequacy of the computer predictions.