MOLECULAR DISSECTION OF A COSMID FROM A GENE-RICH REGION IN 17Q21 ANDCHARACTERIZATION OF A CANDIDATE GENE FOR ALPHA-N-ACETYLGLUCOSAMINIDASE WITH 2 CDNA ISOFORMS

A cosmid mapped to human Chromosome (Chr) 17q21, c140c10, was found to contain a CpC island. We completed the sequence analysis of c140c10 b ecause of two considerations: the cosmid contained an STS from the 17- beta-hydroxysteroid dehydrogenase gene (17-HSD), which was believed to be a neighbor of the breast cancer susceptibility gene, BRCA1; CpG is lands are usually associated downstream and/or upstream of human genes . Computer-based exon trapping of the cosmid sequence revealed putativ e additional exons. With two of those exons used as a probe to screen human placental cDNA libraries, two cDNA isoforms for a novel gene, de signated as ufHSD, were isolated. The amino acid sequence of the open reading frames of the cDNA showed no significant homology to any prote in in the data base. However, it is possible that our cDNAs are from t he gene for alpha-acetylglucosaminidase, which has recently been local ized to the same region. Northern analyses show that the major isoform is expressed in all tissues tested, with the highest expression in bl ood leukocytes and lowest in brain. Finally, our study has shown that the 46.7-kb cosmid c140c10 encompasses loci for five genes and pseudo- genes: Psi PTP4A, ufHSD, 17-HSDI, 17-HSDII, and 22A1.