HUMAN SORBITOL DEHYDROGENASE GENE - CDNA CLONING, SEQUENCE DETERMINATION, AND MAPPING BY FLUORESCENCE IN-SITU HYBRIDIZATION

The cDNA for human sorbitol dehydrogenase (SORD) has been cloned and s equenced. It translates into a peptide of 356 amino acid residues, one more than the sequence previously reported from peptide analysis. An extra alanine was found at the acetyl-blocked N-terminal, between posi tions 1 and 4. This matches the rat cDNA, which also has 356 amino aci ds, with an extra proline at position 3. Four other mismatches were al so observed, but these are all amino acid substitutions that occur out side proposed functionally important regions. Further work must be per formed to determine whether these discrepancies represent polymorphic forms of the enzyme. The SORD gene was mapped by fluorescence in situ hybridization and found to occupy a single site on chromosome 15q15, i ndicating that it is a single-copy gene. This was confirmed by Souther n blot hybridization. SORD is thought to be involved in the etiology o f diabetic complications, and its deficiency has been linked to congen ital cataracts. The cloned gene could be used as a probe to study the role of this enzyme in the pathogenesis of these diseases. (C) 1994 Ac ademic Press, Inc.