Molecular cloning, genomic organization, and chromosomal localization of an additional human aldehyde dehydrogenase gene, ALDH6.
Aldehyde dehydrogenase isozymes have been suggested to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. We previously cloned and characterized four human nonallelic ALDH genes encoding different isozymes. The existence of an unique ALDH isozyme in human saliva and its polymorphism has been demonstrated previously. In this paper, we describe the cloning, characterization, and chromosomal mapping of an aldehyde dehydrogenase gene (ALDH6) expressed in the human salivary gland. The cloned ALDH6 cDNA is 3457 bp in length and contains an open reading frame encoding 512 amino acid residues. The deduced amino acid sequence showed that ALDH6 is larger than the human liver ALDH1 by 11 amino acid residues at the N-terminal, and the degree of identity between the two isozymes is 70% with an alignment of 500 amino acid residues. The human ALDH6 gene spans about 37 kb and consists of 13 exons. The putative TATA and CCAAT boxes and Sp1 binding sites are found in the 5' upstream region of the gene. Northern blot analysis demonstrated that the ALDH6 gene is expressed at low levels in many tissues and at higher levels in salivary gland, stomach, and kidney. The ALDH6 gene was assigned to chromosome 15q26 using fluorescence in situ hybridization.