CLONING AND CHARACTERIZATION OF NOVEL GENE, DCRR1, EXPRESSED FROM DOWNS-SYNDROME CRITICAL REGION OF HUMAN-CHROMOSOME 21Q22.2

The new gene, DCRR1, from the proximal part of the Down's syndrome cri tical region (DCR) was identified by the GRAIL analysis of the 97-kb n ucleotide sequence of two P1 DNAs and the cDNA for DCRR1 gene was clon ed. A 7.36-kb cDNA encodes the imcompleted open reading frame composed of 1941 amino acid residues (220.2 kDa). The deduced amino acid seque nce contains the conserved domain for protein phosphatases at the N-te rminus. The domain encoding the rod-like tail of a myosin heavy chain was also found near the C-terminal region besides the signature for an actin binding protein, profilin, suggesting its possible role as a mi crotuble-associated protein. Two different sizes (7.9 and 9.0 kb) of m RNAs were detected in the poly(A)(+) RNA from abundant tissues by the Northern analysis. The smaller transcript was only transcribed at a hi gh level in the testis. The imbalance of the DCRR1 gene dosage may con tibute to the pathogenesis of Down's syndrome.